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Frontiers in Psychology 2022Random Dot Motion (RDM) displays refer to clouds of independently moving dots that can be parametrically manipulated to provide a perception of the overall cloud moving...
Random Dot Motion (RDM) displays refer to clouds of independently moving dots that can be parametrically manipulated to provide a perception of the overall cloud moving coherently in a specified direction of motion. As a well-studied probe of motion perception, RDMs have been widely employed to understand underlying neural mechanisms of motion perception, perceptual decision-making, and perceptual learning, among other processes. Despite their wide use, RDM stimuli implementation is highly dependent on the parameters and the generation algorithm of the stimuli; both can greatly influence behavioral performance on RDM tasks. With the advent of the COVID pandemic and an increased need for more accessible platforms, we aimed to validate a novel RDM paradigm on Inquisit Millisecond, a platform for the online administration of cognitive and neuropsychological tests and assessments. We directly compared, in the same participants using the same display, a novel RDM paradigm on both Inquisit Millisecond and MATLAB with Psychtoolbox. We found that psychometric functions of Coherence largely match between Inquisit Millisecond and MATLAB, as do the effects of Duration. These data demonstrate that the Millisecond RDM provides data largely consistent with those previously found in laboratory-based systems, and the present findings can serve as a reference point for expected thresholds for when these procedures are used remotely on different platforms.
PubMed: 36562063
DOI: 10.3389/fpsyg.2022.1035518 -
Scientific Reports Apr 2022Non-invasive human brain functional imaging with millisecond resolution can be achieved only with magnetoencephalography (MEG) and electroencephalography (EEG). MEG has...
Non-invasive human brain functional imaging with millisecond resolution can be achieved only with magnetoencephalography (MEG) and electroencephalography (EEG). MEG has better spatial resolution than EEG because signal distortion due to inhomogeneous head conductivity is negligible in MEG but serious in EEG. However, this advantage has been practically limited by the necessary setback distances between the sensors and scalp, because the Dewar vessel containing liquid helium for superconducting quantum interference devices (SQUIDs) requires a thick vacuum wall. Latest developments of high critical temperature (high-T) SQUIDs or optically pumped magnetometers have allowed closer placement of MEG sensors to the scalp. Here we introduce the use of tunnel magneto-resistive (TMR) sensors for scalp-attached MEG. Improvement of TMR sensitivity with magnetic flux concentrators enabled scalp-tangential MEG at 2.6 mm above the scalp, to target the largest signal component produced by the neural current below. In a healthy subject, our single-channel TMR-MEG system clearly demonstrated the N20m, the initial cortical component of the somatosensory evoked response after median nerve stimulation. Multisite measurement confirmed a spatially and temporally steep peak of N20m, immediately above the source at a latency around 20 ms, indicating a new approach to non-invasive functional brain imaging with millimeter and millisecond resolutions.
Topics: Brain; Brain Mapping; Electroencephalography; Humans; Magnetoencephalography; Scalp
PubMed: 35414691
DOI: 10.1038/s41598-022-10155-6 -
Journal of Cell Science Aug 2021The successful investigation of photosensitive and dynamic biological events, such as those in a proliferating tissue or a dividing cell, requires non-intervening... (Review)
Review
The successful investigation of photosensitive and dynamic biological events, such as those in a proliferating tissue or a dividing cell, requires non-intervening high-speed imaging techniques. Electrically tunable lenses (ETLs) are liquid lenses possessing shape-changing capabilities that enable rapid axial shifts of the focal plane, in turn achieving acquisition speeds within the millisecond regime. These human-eye-inspired liquid lenses can enable fast focusing and have been applied in a variety of cell biology studies. Here, we review the history, opportunities and challenges underpinning the use of cost-effective high-speed ETLs. Although other, more expensive solutions for three-dimensional imaging in the millisecond regime are available, ETLs continue to be a powerful, yet inexpensive, contender for live-cell microscopy.
Topics: Electricity; Humans; Imaging, Three-Dimensional; Lens, Crystalline; Lenses; Microscopy
PubMed: 34409445
DOI: 10.1242/jcs.258650 -
Arthroscopy, Sports Medicine, and... Apr 2021To investigate neuromuscular electromyographic response of the of the upper and lower leg muscles after the application of an intraoperative, isolated mechanical...
PURPOSE
To investigate neuromuscular electromyographic response of the of the upper and lower leg muscles after the application of an intraoperative, isolated mechanical stimulus of the capsuloligamentous structures, including the anterior (ACL) and posterior cruciate ligaments (PCL), lateral (LM) and medial menisci (MM), plica mediopatellaris (PM), and Hoffa's fat pat (HFP).
METHODS
The electromyographic response of the upper and lower leg muscles (M. rectus femoris; M. vastus medialis; M. semitendinosus; M. biceps femoris; M. gastrocnemius lateralis) of 15 male patients were measured after an isolated mechanical stimulus of the capsuloligamentous structures during an arthroscopic intervention using a customized intraoperative setup. Target parameters were the short (SLR; <30 milliseconds) and medium latency responses (MLR; >30 milliseconds) after the mechanically-induced trigger.
RESULTS
The ACL, PCL, LM, and MM displayed high interindividual reproducibility of >76%. The MM was the only structure indicating both an SLR and MLR for all muscles. Although signals could be detected, there was no reproducibility in electromyographic signal activation for the HFP. The most rapid MLR was observed for the PM (quadriceps: 37 milliseconds).
CONCLUSIONS
Each stimulated structure displayed an individual MLR response, which allowed us to create neuromapping combining the anatomical and quantitative representations of the individual muscular activation patterns after isolated mechanical stimulation of the capsuloligamentous knee joint structures, corroborating our hypothesis.
LEVEL OF EVIDENCE
Diagnostic - Level II.
PubMed: 34027469
DOI: 10.1016/j.asmr.2020.12.009 -
Biophysical Journal Oct 2020Biological cells deform on a nanometer scale when their transmembrane voltage changes, an effect that has been visualized during the action potential using quantitative...
Biological cells deform on a nanometer scale when their transmembrane voltage changes, an effect that has been visualized during the action potential using quantitative phase imaging. Similar changes in the optical path length have been observed in photoreceptor outer segments after a flash stimulus via phase-resolved optical coherence tomography. These optoretinograms reveal a fast, millisecond-scale contraction of the outer segments by tens of nanometers, followed by a slow (hundreds of milliseconds) elongation reaching hundreds of nanometers. Ultrafast measurements of the contractile response using line-field phase-resolved optical coherence tomography show a logarithmic increase in amplitude and a decreasing time to peak with increasing stimulus intensity. We present a model that relates the early receptor potential to these deformations based on the voltage-dependent membrane tension-the mechanism observed earlier in neurons and other electrogenic cells. The early receptor potential is caused by conformational changes in opsins after photoisomerization, resulting in the fractional shift of the charge across the disk membrane. Lateral repulsion of the ions on both sides of the membrane affects its surface tension and leads to its lateral expansion. Because the volume of the disks does not change on a millisecond timescale, their lateral expansion leads to an axial contraction of the outer segment. With increasing stimulus intensity and the resulting tension, the area expansion coefficient of the disk membrane also increases as thermally induced fluctuations are pulled flat, resisting further expansion. This leads to the logarithmic saturation observed in measurements as well as the peak shift in time. This imaging technique therefore relates the structural changes in the photoreceptor to the underlying neurological function of transducing light into electrical signals. Such label-free optical monitoring of neural activity using fast interferometry may be applicable not only to optoretinography but also to neuroscience in general.
Topics: Action Potentials; Interferometry; Ions; Neurons; Photoreceptor Cells
PubMed: 33031739
DOI: 10.1016/j.bpj.2020.09.005 -
JACC. Clinical Electrophysiology Nov 2022The entrainment response, defined as the difference between the postpacing interval and the tachycardia cycle length (TCL) recorded from a mapping catheter, allows to...
BACKGROUND
The entrainment response, defined as the difference between the postpacing interval and the tachycardia cycle length (TCL) recorded from a mapping catheter, allows to track down the components of the tachycardia loop.
OBJECTIVES
The aim of this study was to evaluate if the postpacing interval measured simultaneously from multiple sites that are remote from the pacing site (PPIR) could be clinically useful in mapping re-entrant circuits.
METHODS
Ninety-two episodes of entrainment response in 29 patients with different macro-re-entrant tachycardias were evaluated using a standardized entrainment protocol. The spatial distribution of different values of PPIR-TCL in a simulation and a computational model of an entrained re-entrant tachycardia was also analyzed.
RESULTS
The PPIR exceeded TCL by more than 20 milliseconds only if both pacing and recording sites were outside the tachycardia circuit. The PPIR-TCL at in-circuit sites was always ≤20 milliseconds. Sites with negative PPIR-TCL values were found either outside or inside the tachycardia circuit.
CONCLUSIONS
Assessment of entrainment response from catheters remote from the pacing site may enhance spatial mapping of the tachycardia circuit. The PPIR-TCL above 20 milliseconds has an excellent positive predictive value in identifying sites outside the tachycardia circuit.
Topics: Humans; Heart Conduction System; Cardiac Pacing, Artificial; Tachycardia, Atrioventricular Nodal Reentry; Computer Simulation; Predictive Value of Tests
PubMed: 36424006
DOI: 10.1016/j.jacep.2022.07.013 -
Journal of Visualized Experiments : JoVE Jun 2022Alpha-synuclein (aSyn) is an intrinsically disordered protein whose fibrillar aggregates are abundant in Lewy bodies and neurites, which are the hallmarks of Parkinson's...
Alpha-synuclein (aSyn) is an intrinsically disordered protein whose fibrillar aggregates are abundant in Lewy bodies and neurites, which are the hallmarks of Parkinson's disease. Yet, much of its biological activity, as well as its aggregation, centrally involves the soluble monomer form of the protein. Elucidation of the molecular mechanisms of aSyn biology and pathophysiology requires structurally highly resolved methods and is sensitive to biological conditions. Its natively unfolded, meta-stable structures make monomeric aSyn intractable to many structural biology techniques. Here, the application of one such approach is described: hydrogen/deuterium-exchange mass spectrometry (HDX-MS) on the millisecond timescale for the study of proteins with low thermodynamic stability and weak protection factors, such as aSyn. At the millisecond timescale, HDX-MS data contain information on the solvent accessibility and hydrogen-bonded structure of aSyn, which are lost at longer labeling times, ultimately yielding structural resolution up to the amino acid level. Therefore, HDX-MS can provide information at high structural and temporal resolutions on conformational dynamics and thermodynamics, intra- and inter-molecular interactions, and the structural impact of mutations or alterations to environmental conditions. While broadly applicable, it is demonstrated how to acquire, analyze, and interpret millisecond HDX-MS measurements in monomeric aSyn.
Topics: Deuterium; Deuterium Exchange Measurement; Hydrogen; Hydrogen Deuterium Exchange-Mass Spectrometry; Protein Conformation; alpha-Synuclein
PubMed: 35815971
DOI: 10.3791/64050 -
Journal of Neurophysiology Sep 2022Neurons are embedded in complex networks, where they participate in repetitive, coordinated interactions with other neurons. Neuronal spike timing is thus predictably...
Neurons are embedded in complex networks, where they participate in repetitive, coordinated interactions with other neurons. Neuronal spike timing is thus predictably constrained by a range of ionic currents that shape activity at both short (milliseconds) and longer (tens to hundreds of milliseconds) timescales, but we lack analytical tools to rigorously identify these relationships. Here, we innovate a modeling approach to test the relationship between oscillations in the local field potential (LFP) and neuronal spike timing. We use kernel density estimation to relate single neuron spike timing and the phase of LFP rhythms (in simulated and hippocampal CA1 neuronal spike trains). We then combine phase and short (3 ms) spike history information within a logistic regression framework ("phaseSH models"), and show that models that leverage refractory constraints and oscillatory phase information can effectively test whether-and the degree to which-rhythmic currents (as measured from the LFP) reliably explain variance in neuronal spike trains. This approach allows researchers to systematically test the relationship between oscillatory activity and neuronal spiking dynamics as they unfold over time and as they shift to adapt to distinct behavioral conditions. Statistical models that incorporate neural spiking history and relationships to the phase of ongoing oscillations in the local field potential robustly capture and predict neuronal engagement in rhythmic processes. These models constitute a powerful tool to systematically test explicit hypotheses regarding the specific rhythmic currents that constrain neural spiking activity over time and during different behaviors.
Topics: Action Potentials; Hippocampus; Models, Neurological; Neurons
PubMed: 35858125
DOI: 10.1152/jn.00423.2021 -
JACC. Clinical Electrophysiology Dec 2022Takotsubo syndrome is associated with life threatening arrhythmias, and the apical ballooning pattern is characterized by a peculiar QT prolongation and particularly... (Review)
Review
BACKGROUND
Takotsubo syndrome is associated with life threatening arrhythmias, and the apical ballooning pattern is characterized by a peculiar QT prolongation and particularly high-risk of arrhythmias.
OBJECTIVES
The aim of the study was to determine the association of QT interval on electrocardiogram for ventricular arrhythmic complications in patients with apical ballooning Takotsubo syndrome in a diverse population at a large urban hospital in the U.S.
METHODS
We reviewed 105 cases of apical ballooning Takotsubo syndrome in patients admitted between 2011 and 2017. Two cardiologists reviewed the electrocardiograms to measure QT interval, adjusted for rate using the Fridericia formula (QTF), and ventricular arrhythmic complications during the hospitalization. Data are reported as median and interquartile range or number and percentage.
RESULTS
Of the 105 patients, 86 (82%) were female, and 34 (32%) were self-reported Black or African American. The mean age was 65 years (range: 58-72 years). Left ventricular ejection fraction was 25% (range: 25%-35%). Heart rate was 101 beats/min (range: 83-121 beats/min). Ten (11%) patients experienced a ventricular arrhythmic complication and had significantly longer QTF (470 [range: 422-543] milliseconds) than did those without complications (417 [range: 383-456] milliseconds, P = 0.031). The area under the curve for QTF was 0.708 (95% CI: 0.536-0.880; P = 0.031). Twenty-eight (27%) patients had a QTF ≥460 milliseconds and significantly more arrhythmic complications (21% vs 5%, odds ratio 4.997 [95% CI: 1.288-19.237], P = 0.021). QTF was an independent predictor of ventricular arrhythmias: odds ratio 1.090 for each 10-millisecond increase in QTF (95% CI: 1.004-1.183; P = 0.040, corrected for sex).
CONCLUSIONS
In a diverse population of patients with apical ballooning Takotsubo syndrome admitted to a large urban hospital in the United States, QTF at admission ≥460 milliseconds identifies patients at high risk for in-hospital arrhythmic complications. Further studies are needed to determine strategies aimed at shortening QT interval to potentially prevent life-threatening arrhythmic events.
Topics: Humans; Female; Aged; Male; Takotsubo Cardiomyopathy; Stroke Volume; Ventricular Function, Left; Long QT Syndrome; Arrhythmias, Cardiac; Hospitals
PubMed: 36543499
DOI: 10.1016/j.jacep.2022.08.010 -
Journal of the American Chemical Society Apr 2022Deciphering the molecular mechanisms of enzymatic allosteric regulation requires the structural characterization of functional states and also their time evolution...
Deciphering the molecular mechanisms of enzymatic allosteric regulation requires the structural characterization of functional states and also their time evolution toward the formation of the allosterically activated ternary complex. The transient nature and usually slow millisecond time scale interconversion between these functional states hamper their experimental and computational characterization. Here, we combine extensive molecular dynamics simulations, enhanced sampling techniques, and dynamical networks to describe the allosteric activation of imidazole glycerol phosphate synthase (IGPS) from the substrate-free form to the active ternary complex. IGPS is a heterodimeric bienzyme complex whose HisH subunit is responsible for hydrolyzing glutamine and delivering ammonia for the cyclase activity in HisF. Despite significant advances in understanding the underlying allosteric mechanism, essential molecular details of the long-range millisecond allosteric activation of IGPS remain hidden. Without using information of the active state, our simulations uncover how IGPS, with the allosteric effector bound in HisF, spontaneously captures glutamine in a catalytically inactive HisH conformation, subsequently attains a closed HisF:HisH interface, and finally forms the oxyanion hole in HisH for efficient glutamine hydrolysis. We show that the combined effector and substrate binding dramatically decreases the conformational barrier associated with oxyanion hole formation, in line with the experimentally observed 4500-fold activity increase in glutamine hydrolysis. The allosteric activation is controlled by correlated time-evolving dynamic networks connecting the effector and substrate binding sites. This computational strategy tailored to describe millisecond events can be used to rationalize the effect of mutations on the allosteric regulation and guide IGPS engineering efforts.
Topics: Allosteric Regulation; Aminohydrolases; Binding Sites; Glutamine
PubMed: 35412310
DOI: 10.1021/jacs.1c12629